GALC

galactosylceramidase, the group of Glycoside hydrolases

Basic information

Region (hg38): 14:87837820-87993665

Links

ENSG00000054983 ∙ NCBI:2581 ∙ OMIM:606890 ∙ HGNC:4115 ∙ Uniprot:P54803 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Strong), mode of inheritance: AR
• Krabbe disease (Strong), mode of inheritance: AR
• Krabbe disease (Strong), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Krabbe disease	AR	Biochemical	BMT/HSCT have been described, and in presymptomatic infants as well as older mildly-affected individuals, this treatment may improve and preserve cognitive function (ie, presymptomatic transplant has much better neurological outcomes)	Biochemical; Neurologic	14024503; 3123790; 4773865; 1817026; 1817027; 2056315; 1891085; 8297359; 7581365; 9449482; 8940268; 9338580; 9545360; 10833326; 15901860; 16607461; 17579360; 19332366; 21070211; 20301416; 20886637; 22115770; 22704718; 23462331; 23276707; 33832819

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GALC gene.

• Galactosylceramide beta-galactosidase deficiency (114 variants)
• not provided (20 variants)
• GALC-related disorder (2 variants)
• Inborn genetic diseases (2 variants)
• Abnormality of the nervous system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	288	9	301
missense	15	81	236	6	5	343
nonsense	29	35				64
start loss		4	1			5
frameshift	63	48				111
inframe indel	2	1	4			7
splice donor/acceptor (+/-2bp)	10	40				50
splice region	1	3	22	69	9	104
non coding			25	164	89	278
Total	119	209	270	458	103

Highest pathogenic variant AF is 0.0000276

Variants in GALC

This is a list of pathogenic ClinVar variants found in the GALC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-87925139-C-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Oct 10, 2017)
14-87925152-T-C		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Aug 25, 2017)
14-87925176-G-A		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Aug 30, 2017)
14-87933107-T-C		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933134-C-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 12, 2018)
14-87933144-A-C		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 12, 2018)
14-87933148-C-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 12, 2018)
14-87933274-A-G		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933279-T-C		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 13, 2018)
14-87933281-G-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933457-C-T		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 12, 2018)
14-87933543-TATC-T		Galactosylceramide beta-galactosidase deficiency	Benign (Jun 14, 2016)
14-87933606-C-T		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 12, 2018)
14-87933733-A-G		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933738-G-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933743-C-T		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 13, 2018)
14-87933855-A-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87933931-T-A		Galactosylceramide beta-galactosidase deficiency	Likely benign (Jan 13, 2018)
14-87934009-C-T		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 12, 2018)
14-87934023-T-G		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 12, 2018)
14-87934105-T-C		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 13, 2018)
14-87934106-G-A		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 13, 2018)
14-87934141-C-T		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)
14-87934142-A-G		Galactosylceramide beta-galactosidase deficiency	Benign (Jan 13, 2018)
14-87934233-A-G		Galactosylceramide beta-galactosidase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALC	protein_coding	protein_coding	ENST00000261304	17	155846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.21e-15	0.762	124685	0	113	124798	0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.186	365	375	0.973	0.0000193	4447
Missense in Polyphen		124	149.03	0.83204		1770
Synonymous	-0.0698	136	135	1.01	0.00000715	1286
Loss of Function	1.88	29	42.2	0.687	0.00000216	461

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000782	0.000781
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000278	0.000278
Finnish	0.000467	0.000464
European (Non-Finnish)	0.000497	0.000494
Middle Eastern	0.000278	0.000278
South Asian	0.000459	0.000458
Other	0.000497	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon. {ECO:0000269|PubMed:8281145, ECO:0000269|PubMed:8399327}.
• Disease: DISEASE: Leukodystrophy, globoid cell (GLD) [MIM:245200]: An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death. {ECO:0000269|PubMed:10234611, ECO:0000269|PubMed:10477434, ECO:0000269|PubMed:17579360, ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:23462331, ECO:0000269|PubMed:8595408, ECO:0000269|PubMed:8786069, ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.449

Intolerance Scores

• loftool: 0.252
• rvis_EVS: 0.85
• rvis_percentile_EVS: 88.48

Haploinsufficiency Scores

• pHI: 0.0687
• hipred: N
• hipred_score: 0.474
• ghis: 0.434

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.407

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Galc
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: galactosylceramide catabolic process;glycosphingolipid metabolic process;myelination
• Cellular component: lysosome;lysosomal lumen
• Molecular function: galactosylceramidase activity